Our theoretical framework has to do with the fact that many behavioral manifestations of drug use and abuse are not immediate or acute; they occur over time. We focus on prompt and delayed neurobiological responses to drug administration and their relevance to states of sensitivity, tolerance, habitual use, and addiction. We are concentrating on catecholaminergic and serotonergic systems in the brain, more specifically, on two neurologically distinct systems, the mesolimbic and the nigrostriatal. With quantitative microspectrofluorometric techniques we are beginning to evolve a biochemical anatomy of the brain apart from the anatomy described by histofluorescence alone. We're able to manipulate several regulatory mechanisms affecting the function of the key transmitter synthesizing enzymes in these pathways, and we're also elucidating metabolic degradative pathways for drugs and amines within the brain. We are developing behavioral and electrophysiological techniques of observation and correlating data from them with central chemical measurements. We are trying to evolve a comprehensive model for the direct and indirect, short-term and long-term effects of amphetamines on mesolimbic and nigrostriatal systems in the brain and their associated behaviors.